Extracellular DDR1 targeting remodels collagen-rich tumor stroma and local immunity

DDR1nb 3 Fc, a cross-reactive extracellular DDR1 nanobody Fc, achieves tumor control in immunocompetent mammary and pancreatic models, including an orthotopic pancreatic model.

• Why it matters: Collagen-rich stroma can block immune-cell entry and maintain immune exclusion, yet direct ways to target extracellular matrix organizing receptors are limited.
• What they did: The study engineered cross-reactive DDR1 nanobody Fc proteins and tested DDR1nb 3 Fc in immunocompetent mammary and pancreatic tumor models, using single-cell profiling plus compositional and pseudobulk pathway analyses.
• The result: Tumor control aligns with altered collagen architecture and intratumoral immune remodeling, with pathway-level changes in tumor-associated neutrophils and Ly6G-positive depletion significantly modifying DDR1nb 3 Fc’s antitumor effect.

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